Role of cftr in chloride secretion across human tracheal epithelium. Shen, B-Q., R. J. Mrsny, W. E. Finkbeiner, and J. H. Widdicombe. Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA 94143, Genentech Inc., South San Francisco, CA 94080, and Children's Hospital of Oakland Research Institute, Oakland, CA 94609
APStracts 2:0091L, 1995.
We have tested two hypotheses: 1) the cystic fibrosis transmembrane conductance regulator (CFTR) represents the predominant Cl conductance in the apical membrane of human tracheal epithelium, and 2) CFTR in this tissue is close to maximally activated under baseline conditions. In support of the first hypothesis we found: 1) When the level of differentiation of cultures was varied by varying the culture conditions, there was a significant positive correlation between the levels of CFTR and the magnitude of mediator-induced Cl secretion. 2) Amiloride-insensitive baseline Isc and mediator-induced increases in Isc were inhibited by diphenylamine-2-carboxylate acid (DPAC) but not by 4,4'-diisothiocyanato stilbene-2,2' disulfonate (DIDS), a pharmacology consistent with passage of apical membrane Cl current through CFTR; Ca-activated Cl channels are inhibited by DIDS but not DPAC. 3) Raising temperature from 22 to 37 oC increased 125I efflux, and this increase was inhibited by DPAC and blockers of protein kinase A, but not by DIDS or BAPTA-AM. In support of the second hypothesis we have earlier (Yamaya et al. 1992. Am. J. Physiol. 262:L713-L724) shown that cAMP-elevating agents are essentially without effect on Isc across primary cultures of human tracheal epithelium. Here, we further show that these agents are also usually without effect on 125I efflux; the mean increase in efflux in response to elevating cAMP was 20 % that of raising temperature from 22 to 37 oC. 

Received 29 April 1994; accepted in final form 10 May 1995.
APS Manuscript Number L125-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.